Rheumatoid arthritis, systemic lupus erythematosus, and systemic scleroderma can all involve the joints, muscles, and bones but have distinct patterns of involvement. Rheumatoid arthritis predominantly affects the small joints of the hands and feet symmetrically, leading to erosions, deformities, and joint destruction. Systemic lupus erythematosus usually causes non-deforming arthritis or arthralgia that can be migratory or asymmetric, with normal joint spaces but subchondral sclerosis and osteopenia. Systemic scleroderma is characterized by soft tissue calcification, acro-osteolysis of the distal phalanges, and flexion contractures resulting from

1. Differential diagnosis of joint, muscle and bone
involvement in rheumatoid arthritis, systemic lupus
erythematous, and systemic scleroderma

2. Overview
 Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that affects many organs but more
predominantly synovial tissue and joints, manifesting with symmetric, inflammatory, peripheral polyarthritis.
It typically leads to deformity and destruction of joints through the erosion of cartilage and bone.
 Arthritis symptoms typically first develop in the hands and wrists in a symmetric, proximal distribution. Feet
and large joints may also be involved.
 Epidemiology: overall world prevalence is approx. 1%. With a female to male ratio of 3:1, ages 30-50
 Pathogenesis: IgM autoantibodies to FC portion of IgG, forming immune complexes which deposit in joints
resulting in inflammation.
 Clinical features:
 Musculoskeletal pain which decreases with activity, tenderness, swelling, subcutaneous nodules, morning
stiffness >30minutes
 Polyarthritis of MCP and PIP joints, but it commonly does NOT involve DIP joints. Wrists, elbows, ankles, knees
also commonly are involved.
 Persistent symmetric polyarthritis (synovitis) of hands and feet (hallmark feature)
 affected joints show inflammation with swelling, tenderness, warmth, and decreased range of motion (ROM).
 Joint and tendon destruction may lead to deformities such as ulnar deviation, boutonniere and swan neck
deformities, hammertoes, and occasionally, joint ankylosis.
 Other commonly observed manifestations: tenosynovitis, periarticular osteoporosis, carpal tunnel syndrome,
generalized osteoporosis

3. The radiographic hallmarks of rheumatoid
arthritis are:
 erosions; important early finding, frequently in the radial side of the metacarpophalangeal
(MCP) joints
 Soft tissue swelling: fusiform and periarticular; represents a combination of joint effusion,
edema, and tenosynovitis. This can be an early/only radiological finding.
 Osteoporosis; initially juxta-articular and later generalized
 Symmetrical or concentric joint space narrowing
Hands and Wrists Involvement
 The disease tends to affect the proximal joints in a bilateral, symmetrical distribution.
 PIP and MCP joints (specially 2nd and 3rd MCP)
 Ulnar styloid
 Triquetrum
 DIP joints are spared

4.  Late changes include:
 Subchondral cyst
 Subluxation causing: a) ulnar deviation of MCP joints, b) boutonniere and swan neck deformities
 Hitchhiker’s thumb deformity
 Carpal instability, ulnar translocation
 Anykylosis
 Scallop sign; erosion of ulnar aspect of distal radius
Feet
 similar to the hands, there is a predilection for the PIP and MTP joints (specially 4th and 5th MTP)
 Involvement of subtalar joint
 Hammertoe deformity
 Hallux valgus

5. Knee
 Joint effusion
 Typically involves lateral or non-weight bearing portion of the joint
 Loss of joint space involving all three compartments
 Prepatellar bursitis
Hip
 Concentric loss of joint space
 Acetabular protrusio
Shoulder
 Erosion of distal clavicle, marginal erosions of humeral head, reduction in acromiohumeral
distance “high-riding shoulder” due to subacromial-subdeltoid bursitis
Spine
 Cervical spine is more frequently involved in RA, thoracic and lumbar involvement is rare.
 Findings include: erosions, atlantoaxial subluxation

6.  Diagnosis of RA is based on the diagnostic criteria developed by American college of
rheumatology 2010. A total score of 6+ is classified as rheumatoid arthritis.
 Investigations include:
 CPR and ESR (elevated)
 Serological markers: RF, anti-CCP, ACPA
 Radiography: erosions, swelling of soft tissue, joint narrowing, juxtoarticular
osteoporosis
 Ultrasound: assess synovial proliferation and inflammation of superficial
joints, tenosynovitis, bursitis
 MRI: sensitive to early and subtle features of RA

9. Advanced RA

10. Typical changes in RA, MCP osteopenia, marked erosions

13. Degenerative changes with marked erosions

14. Scallop sign

16. SLE
 Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune inflammatory
disease that can affect any part of the body. SLE is a disease of unknown aetiology with a
variety of presenting features and manifestations. Characterized by microvascular
inflammation with the generation of numerous autoantibodies, particularly antinuclear
antibodies (ANA)
 The majority of the pathology in SLE is related to deposits of immune complexes in
various organs, which triggers complement and other mediators of inflammation
 Diagnosis can be difficult because lupus mimics many other diseases; it requires clinical
and serologic criteria.
Epidemiology
 Female:Male 10:1
 Peak in 20s-30s
 More common in black patients

17.  Musculoskeletal manifestations: joint pain, with small joints of the hand and wrist usually
affected. Arthralgia, arthritis, osteonecrosis (avascular necrosis of bone), and myopathy are
the principal manifestations.
 Arthralgia, myalgia, and frank arthritis may involve the small joints of the hands, wrists, and
knees
 In contrast to rheumatoid arthritis, SLE arthritis or arthralgia may be asymmetrical, with
pain that is disproportionate to swelling. Also the arthritis and arthralgia of SLE tend to be
migratory, morning stiffness is usually measured in minutes. The arthritis of SLE is generally
considered to be non-deforming.
 Involves joint space loss, subchondral sclerosis, osteophyte, and ulnar deviation of the
phalanges without erosions such as in RA
Diagnosis is based on SLICC Classification Criteria 2012. Requirements: >4 of the following
criteria (at least 1 clinical and 1 laboratory) OR biopsy proven lupus nephritis with positive ANA
or Anti-dsDNA

18.  Clinical criteria
 Malar rash bullous lupus, photosensitivity
 Discoid rash, hypertrophic lupus
 Oral ulcers or nasal ulcers
 Non-scarring alopecia
 Synovitis
 Serositis
 Nephritis
 Cerebritis, myelitis, neuropathy
 Hemolytic anemia
 leukopenia or lymphopenia
 Thrombocytopenia
 Immunological criteria
 ANA
 Anti-dsDNA
 Anti-Sm
 Antiphospholipid antibody
 Low complement C3, low C4
 Direct Coombs' test in the absence of haemolytic anaemia

19. Musculoskeletal manifestations
 Symmetric polyarthritis: represents the most common presenting complaint clinically. Usully worse in the morning.
Areas of involvement most commonly are the small joints of hands, wrists (PIP, MCP), knees, and shoulders
 Tenderness, edema, and effusions accompany a polyarthritis that is symmetric, nonerosive, and usually
nondeforming.
 Characteristic hand deformities are swan neck deformities that result from recurrent synovitis and inflammation of
the joint capsule, tendons, and ligaments. These deformities are usually reducible and nonerosive.
 Deforming non-erosive arthropathy: due to ligamentous laxity and muscle contracture, not articular destruction.
More common in long-standing disease. Non-erosive arthritis involving two or more joints can be diagnostic. The
presence of deformities without erosions differentiates it from rheumatoid arthritis. It develops approx. in 5-40% of
patients when articular abnormalities are present.
 Myositis: clinically observed in 30-50% of patients.
 Jaccoud arthropathy is the term used to describe the nonerosive hand deformities due to chronic arthritis and
tendonitis that develop in 10% of patients with SLE.
 The most common radiographic anomalies in SLE are periarticular osteopenia and soft-tissue swelling without
erosions.
Radiographic features
 Demonstrates soft tissue swelling of the involved joints(interphalangeal joints is most common), periarticular
osteoporosis, and normal joint spaces. Carpal instability may be seen in 15% of patients
 Osteonecrosis – most common location is femoral head – manifests as focal pain
 Calcifications linear or nodular calcification in the subcutaneous and deep soft tissues may be seen, specially around
small joints of extremities.
 Stress fractures
 Osteomyelitis and septic arthritis

20.  Tendinopathies: include tenosynovitis, bursitis, spontaneous tendon weakening and eventually
rupture, more affecting weight-bearing joints as a complication of steroid therapy. Imaging
features also include capsular swelling, edematous and proliferative tenosynovitis and synovial
hypertrophy
 Subcutaneous nodules: particularly over flexor tendons of the hands
Diagnosis is based on clinical presentation, ANA screening, imaging findings, ACR diagnostic
criteria, and lab tests including: CBC, antiphospholipid antibodies, anti-dsDNA, and anti-Sm
antibodies, ESR(elevated), CPR (normal in flare ups).
Treatment
Hydroxychloroquine is recommended in all patients
NSAIDS to manage arthralgia
Corticosteroids, dose depends on severity, but they are given for short time to minimize side
effects
Methotrexate and azathioprine should be considered in case of poor symptom control after a trial
of corticosteroids and hydroxychloroquine.

23. Scleroderma systemic
 Scleroderma is an autoimmune connective tissue disorder characterized by multisystem fibrosis and
soft tissue calcification.
 There are two primary types of scleroderma: localized and systemic (also called systemic sclerosis).
 The disease is characterized by widespread deposition of collagen and other extracellular matrix
proteins. Occurs as a result of an abnormal immune response. Small vessels are involved early in the
disease, accounting for the involvement of organs with a dense capillary network. This results in
perivascular fibrosis and gradual luminal stenosis.
 Raynaud phenomenon occurs in almost all patients with systemic sclerosis
Musculoskeletal Manifestations
 Scleroderma may affect joints (arthritis, arthralgia), tendons (rubs, tenosynovitis) and muscles
(myalgia, weakness, more rarely myositis). Friction tendon rubs, seen on the hands, knees, and
ankles, indicate a poor prognosis. Digital retractions in flexion due to skin sclerosis and calcinosis,
lead to major functional disorders.
 Limitation of movement, and joint swelling may be present. Systemic sclerosis begins as joint pain in
15% of patients. It begins as inflammatory myopathy in 10% of patients. Weakness is present in 80%
of patients

24. ACR diagnostic criteria for systemic sclerosis

25. Musculoskeletal features
 Phalangeal changes consisting of bone absorption, skin atrophy, and soft tissue
calcification. These features are classic, and their presence alone should suggest the
correct diagnosis. In some cases however the joint changes predominate. The wrist is
frequently involved. The interphalangeal joints are also affected but to a lesser degree
and in an asymmetric manner.
 The presence of soft tissue calcification is extremely important. It’s rarely seen in
rheumatoid arthritis or SLE. When identified, soft tissue calcification is therefore
considered diagnostic for scleroderma and in some patients is the only differential
feature.

26. Musculoskeletal manifestations
Radiographic features
 Bone changes
 Acro-osteolysis (resorption of the distal phalanges)
 Periarticular osteopenia
 Joint space narrowing
 Erosions
 Severe resorption of the first CMC joint with radial subluxation is a characteristic
feature on hands radiographs
 Soft tissue changes
 Subcutaneous and periarticular calcification
 Atrophy, specially at tips of fingers
 Flexion contractures

27.  Other less common documented musculoskeletal findings:
 rib resorption (bilateral superior rib notching, predominantly along posterior surface),
mandibular angle resorption (+/- loss of lamina dura), radius and ulnar resorption
 Terminal phalangeal sclerosis
 Serological markers
 Elevated ESR
 RF – positive in 30-40% of patients
 Antinuclear antibodies – 35-95% of patients
 Anti SCL-70: positive in 30-70% of patients, particularly in limited disease
 Anti-centromere antibodies (20-40% of patients, in limited disease particularly)

28. Musculoskeletal symptoms treatment
 Carpal tunnel syndrome symptoms may require local corticosteroid injections although
frequently these symptoms resolve spontaneously.
 Myositis may be treated cautiously with steroids (first choice), or with methotrexate or
azathioprine in corticosteroid-resistant cases or when there are contraindications to
corticosteroid use. Doses of prednisone greater than 40 mg/d are associated with a higher
incidence of scleroderma-associated renal crisis.
 Arthralgia’s can be treated with acetaminophen and nonsteroidal anti-inflammatory drugs
(NSAIDs).

29. Acro-osteolysis and soft tissue calcifications

30. Multiple soft tissue calcifications, joints
destruction, ankyloses of 2nd finger DIP.

31. Calcifications of subcutaneous tissue

32. Extensive soft tissue calcifications and
osteoporosis

33. Bibliographies
www.medscape.com
www.ncbi.nlm.nih.gov
radiopaedia.org
www.aafp.org
wikem.org
www.uptodate.com
sclerodermanews.com